Rapolas Jamontas has defended his thesis entitled "Demodification by TudS Proteins: From Individual Thionucleobases to Intact tRNA" for the degree of Doctor of Science in Biochemistry.
Scientific supervisors:
Prof. Dr. Rolandas Meškys (Vilnius University, Natural Sciences, Biochemistry) from October 01, 2020, till December 18, 2023; Dr. Agota Aušynaitė (Vilnius University, Natural Sciences, Biochemistry) from December 19, 2023, till September 30, 2024.
Scientific consultants:
Dr. Agota Aušynaitė (Vilnius University, Natural Sciences, Biochemistry) from October 01, 2020, till December 18, 2023; Prof. Dr. Rolandas Meškys (Vilnius University, Natural Sciences, Biochemistry) from December 19, 2023, till September 30, 2024;
Composition of the Dissertation Defence Board: Chairperson - Pof. D. Eglė Lastauskienė (Vilnius University, Natural Sciences, Biology); Dr. Dukas Jurėnas (French National Centre for Scientific Research, France, Natural Sciences, Biochemistry); Dr. Patrick Pausch (Vilnius University, Natural Sciences, Biochemistry); Dr. Jūratė Skerniškytė (Vilnius University, Natural Sciences, Biochemistry); Dr. Miglė Tomkuvienė (Vilnius University, Natural Sciences, Biochemistry).
One of the most commonly found sulfur-modified nucleosides in prokaryotes is 4-thiouridine (s4U), located at the 8th position of tRNA. This modification helps prokaryotic tRNA maintain thermodynamic stability. Additionally, due to its photoreactivity, s4U nucleoside can function as an ultraviolet (UV) sensor. Previous studies have shown that the TudS protein family, widespread in prokaryotes, acts as thiouracil desulfurases; however, neither their specificity nor the activity of the widespread TudS-DUF1722 (RudS) fusion protein has been elucidated. In this dissertation, TudS and RudS proteins were biochemically characterized, and their potential physiological function in the metabolism of thiomodified nucleosides and bacterial UV stress response was proposed. Additionally, a role in tRNA interaction was suggested for the previously uncharacterized domain of unknown function 1722 (DUF1722) found in RudS proteins. Proteins containing a single TudS domain were characterized as 4-thio-UMP desulfurases, potentially involved in tRNA catabolism. Furthermore, the study demonstrated that TudS proteins help bacteria utilize exogenous 4-thiouracil derivatives as a source of uracil, thereby detoxifying the growth environment. RudS proteins, composed of fused TudS and DUF1722 domains, were biochemically and bioinformatically identified as enzymes that interact with tRNA and demodify 4-thiouridine. The study demonstrated that this demodification process enables bacteria to adapt more rapidly to UV stress and may be associated with stress response mechanisms.
 |